BACKGROUND: When lung cancer is combined with concurrent tuberculosis (TB), it increases the difficulty of diagnosis and treatment, leading to missed and/or misdiagnosed cases.
OBJECTIVE: To provide reference markers for the clinical diagnosis of patients with lung cancer complicated by active pulmonary TB (APT).
METHODS: The concentration of survivin in diseased tissue, and miR-29a and IGRAs interferon gamma (IFN-γ) in serum were evaluated in 25 patients with non-small cell lung carcinoma (NSCLC) complicated by APT, 32 patients with NSCLC and 30 patients with APT.
RESULTS: The expression of miR-29a in serum of patients with APT was higher than in patients with NSCLC complicated by APT (least significant difference (LSD)-t = 4.724, p < 0.001), and the NSCLC group (LSD-t = 6.619, p < 0.001). Furthermore, patients with NSCLC complicated by APT had higher miR-29a concentration than the NSCLC group. The rate of positive survivin expression in NSCLC (χ2 = 23.418, p < 0.001) and NSCLC combined with APT group (χ2 = 17.160, p < 0.001) was significantly higher than in patients with APT. The concentration of IFN-γ in serum of the NSCLC complicated by APT group (LSD-t = 2.912, p = 0.004) and the APT group (LSD-t = 4.452, p < 0.001) was higher than in the NSCLC group. The level of IFN-γ in serum of the NSCLC complicated by APT group were higher than in the APT group, but there was no statistical difference.
CONCLUSIONS: The levels of MiR-29a, Survivin and IFN-γ was helpful for differential diagnosis of lung cancer and tuberculosis.

There is an urgent need for precise diagnosis to distinguish nontuberculous mycobacterial (NTM) diseases from pulmonary tuberculosis (PTB) and other respiratory diseases. The aim of this study is to evaluate the diagnostic performance of Interferon-gamma (IFN-γ) release assays (IGRAs), including antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT.TB) and QuantiFERON-TB-Gold-Test (QFT-G), in differentiating NTM infections (N = 1,407) from culture-confirmed PTB (N = 1,828) and other respiratory diseases (N = 2,652). At specie level, 2.56%, 10.73%, and 16.49% of NTM-infected patients were infected by Mycobacterium kansasii, M. abscessus, and with M. avmm-intracellulare complex (MAC), respectively. Valid analyses of T-SPOT.TB (ESAT-6, CFP-10) and QFT-G were available for 37.03% and 85.79% in NTM-infected patients, including zero and 100% (36/36) of M. kansasii infection, 21.85% (33/151) and 92.05% (139/151) of M. abscessus infection, and 17.67% (41/232) and 91.24% (211/232) of MAC infection. Based on means comparisons and further ROC analysis, T-SPOT.TB and QFT-G performed moderate accuracy when discriminating NTM from PTB at modified cut-off values (ESAT-6 < 4 SFCs, CFP-10 < 3 SFCs, and QFT-G < 0.667 IU/ml), with corresponding AUC values of 0.7560, 0.7699, and 0.856. At species level of NTM, QFT-G effectively distinguished between MAC (AUC=0.8778), M. kansasii (AUC=0.8834) or M. abscessus (AUC=0.8783) than T-SPOT.TB. No significant differences in discriminatory power of these three IGRA tools were observed when differentiating NTM and Controls. Our results demonstrated that T-SPOT.TB and QFT-G were both efficient methods for differentiating NTM disease from PTB, and QFT-G possessed sufficient discriminatory power to distinguish infections by different NTM species.

The interferon-γ release assays as potent adjunct tools for the quick detection of TB in high burden countries is feasible. In this retrospective study, we aimed to identify the risk factors for negative T-SPOT results in confirmed active tuberculosis.
We consecutively enrolled 1,021 patients who were positive for acid-fast bacilli smear staining or culture-confirmed mycobacterial infection and simultaneously tested with the T-SPOT.TB assay. All of the included specimens were used to discriminate the Mycobacterium species using the biochip assay. We collected basic clinical characteristics and laboratory results for further analysis.
Of the 1,021 patients enrolled in the study, 89 patients were identified as having nontuberculous mycobacteria (NTM). Ninety-nine patients were excluded from the analysis because of indeterminate T-SPOT.TB results, while the remaining 833 patients were identified as having Mycobacterium tuberculosis infection. In total, 159 patients had false-negative T-SPOT.TB results (19.1% of 833). The concordance rate between the T-SPOT.TB results and final diagnoses in females was always lower than that in males. Multivariate logistic regression analysis showed that female sex (OR 1.81; 95% CI 1.19, 2.7; p = 0.006), age (OR 1.02; 95% CI 1.01, 1.03; p = 0.003), acid-fast bacilli (AFB) smear-negative (OR 5.45; 95% CI 3.62, 8.19; p < 0.001), HIV coinfection (OR 6.83; 95% CI 2.73, 17.10; p < 0.001) were associated with negative T-SPOT.TB result.
Female is another independent risk factor of negative T-SPOT.TB results, besides to elder, HIV co-infection, acid-fast bacilli (AFB) smear-negative who are suspected of having active TB infection.

BACKGROUND: This study aimed to determine whether increased cut-off of the T-SPOT.TB could aid in diagnosing active tuberculosis (ATB).
METHODS: Patients suspected of having TB were enrolled to derive a T-SPOT.TB threshold value to help diagnose ATB, which was subsequently validated in real-world clinical practice.
RESULTS: In total, 701 adult patients suspected of having tuberculosis who had undergone the T-SPOT.TB assay were included in the derivation cohort. The numbers of ESAT-6 (U = 43583, P = 0.0002) and CFP-10 (U = 41753, P < 0.0001) spot-forming cells (SFCs) significantly increased in the ATB group compared with the Latent tuberculosis infection (LTBI) group. According to receiver operating characteristic analysis, when a cut-off of 37.5 SFCs/2.5 × 105 cells was used to discriminate between ATB and LTBI, the sensitivity was 57.5% (95% confidence interval [CI] 50.7%-64.2%) and the specificity was 59.8% (95% CI 55.2%-64.2%). A threshold value of 173.5 SFCs/2.5 × 105 could be used to obtain a specificity of <90% to discriminate between ATB and LTBI. The diagnostic accuracy of higher T-SPOT.TB threshold values in the validation cohort was similar to that in the derivation cohort.
CONCLUSIONS: In high-burden countries, a higher threshold value of 173.5 SFCs/2.5 × 105 may aid in ATB diagnosis in suspected tuberculosis patients.

To evaluate the performance of QuantiFERON-TB Gold Plus (QFT-Plus) on Mycobacterium tuberculosis (MTB) infection test among registered village doctors from China.
MTB infection of the registered village doctors in Zhongmu County were tested using QFT-Plus and two other interferon-gamma release assays (IGRAs) in parallel: QuantiFERON-TB Gold In-Tube (QFT) and T-SPOT.TB (T-SPOT). Retests were carried out for baseline positives at 3 and 6 months later, respectively.
A total of 616 village doctors were included in the baseline examination. The positivity of QFT, QFT-Plus and T-SPOT was 27.91% (168/602), 31.22% (187/599) and 27.70% (169/610), respectively. The concordance between QFT and QFT-Plus was 94.81% (Kappa coefficient: 0.87) and between T-SPOT and QFT-Plus was 88.93% (Kappa coefficient: 0.73). Reversions were frequently observed for all three assays. With respect to QFT-Plus, the quantitative results of reversions in the serial testing were mostly distributed in an \"uncertain range\" zone (0.2-0.7 IU/mL). Similar patterns of distribution were observed for QFT and T-SPOT as well.
Village doctors should gain more attention as an at-risk group for TB infection control in rural China. Our results support, by means of serial testing, a good agreement between QFT-Plus and QFT in Chinese population.

Interferon-gamma release assays (IGRAs) have been demonstrated to be useful in the diagnosis of Mycobacterium tuberculosis (MTB) infection. However, IGRAs have not been recommended for clinical usage in most low-income countries due to the shortage of clinical data available resulting from their high test cost. Recently, a cheaper domestic TB-IGRA was approved in China. In this study, we compared TB-IGRA with QuantiFERON-TB Gold In-Tube (QFT-GIT) for MTB infection diagnosis in 253 active TB patients, 48 non-TB lung disease patients, 115 healthcare workers and 216 healthy individuals. The proportion of positive TB-IGRA results in active TB patients, patients with non-TB lung disease, healthcare workers and healthy individuals was 88.3%, 27.1%, 40.9% and 17.6%, respectively, which was similar to the results of QFT-GIT, with an overall agreement of 95% (κ = 0.89) and a high correlation between their responses (r = 0.85, p < 0.001) being observed. In conclusion, the TB-IGRA has comparable clinical performance with QFT-GIT.